Evaluating Thiourea Architecture for Intramolecular [2+2] Photocycloaddition of 4‐Alkenylcoumarins

Abstract

The efficiency of [2+2] photocycloadditions of 4-alkenylcoumarins was evaluated with various thiourea skeletons to develop thiourea-based catalysts for promoting photochemical reactions. Our results indicate that the excited state chemistry is dependent on the nature of the thiourea catalyst employed to activate the photoactive substrate.Keywords: asymmetric photoreactions; hydrogen bonding photocatalysis; organophotocatalysis; photochirogenesis; thiourea photocatalysis Photochemical transformations are an important class of organic reactions that are often known to generate products with unique stereochemistry.[1] For this reason, chemists have developed strategies that are readily applied in organic synthesis.[2] In recent years, there has been tremendous impetus towards developing enantioselective syntheses of complex strained compounds by light initiated reactions. [1c,2i] In that regard three different catalytic strategies have garnered attention, as they are effective in controlling chemical transformations initiated by light. The first strategy involves photoredox chemistry [3] where a light absorbing sensitizer performs a one electron oxidation or reduction of the reactive substrate leading to a radical anion or a radical cation. As these reactive species are in the ground state, their higher potential enables them to react efficiently to form products. The second strategy involves an energy transfer mechanism [2h,4] where the excited state energy from a light absorbing sensitizer is transferred to the substrate, producing a singlet or a triplet excited state that reacts to form the product. This strategy requires the excited state energy of the sensitizer to be higher than that of the reactive substrate. The third strategy involves an energy sharing mechanism where, upon light excitation, the sensitizer/catalyst and reactant complex (static/dynamic complex) undergo a phototransformation to form the product(s). [5] We have embraced the energy sharing strategy and have utilized thiourea-based catalysts [6] to promote photoreactions with excellent control of product enantioselectivity.[5b] As an example, we showed that 4-alkenylcoumarin 1a underwent a stereoselective [2+2] photocycloaddition to form photoproduct 2a with 94% enantioselectivity with binaphthyl based thiourea catalysts.[5b] Having deciphered the importance of binaphthyl based thiourea catalysts we were interested in evaluating other thiourea skeletons to promote photochemical transformations. We were interested in the role of thioureas not only to achieve high enantioselectivity but also high conversions, as it will increase the type of skeletons that could be employed for controlling photoreactions. In this report we present our findings with six diverse thiourea catalysts 3b-g in promoting the [2+2] photocycloaddition of coumarins 1a and 1b. (Scheme 1). The efficiencies of the new thiourea skeletons were compared to reaction efficiency with our previously established catalyst 3a (prepared in one step from commercially availab...

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